BMP signaling pathway in eyelid development (WP3663)

The signaling pathways involved in eyelid development are displayed with interactions that are known (solid arrows) and proposed (dotted arrows). The four main pathways shown are activated by Fgf10 and regulate key processes, but also interact with each other. The first pathway is a proposed promotion of sfrp1 which inhibits Wnt that regulates the Meibomian Gland. The Wnt pathway also activates pitx2 and begins the proposed pathway to eyelid closure. The second pathway begins with Fgfr2 activating Bmp4, a protein that may also be regulated by Shh, and continuing through a protein chain to regulate conjunctival cell fate. In this pathway Bmp also inhibits transdifferentiation of Meibomian Gland into a hair follicle, conjunctiva proliferation, and precocious differentiation. The last two pathways are linked to the regulation of eyelid closure through a cascade of protein activation and is further promoted by Bmp through stimulation of phosphorylated c-Jun. This pathway is based on figure 10B from Huang et al.

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